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Between March 5 and July 25, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10 090 corresponding to a cumulative incidence rate of 285.7 per 100 000 population. Demographic and clinical information on all the cases along with exposure and contact information was collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number Rt and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0 % (790/5646) in Federation of Bosnia and Herzegovina (FBH) and 6.2 % (267/4299) in Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the basic reproduction number increased from 1.13 on May, the 20th to 1.72 on May the 31st. The outbreak concerns both entities, Federation of Bosnia and Herzegovina and Republika Srpska, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.

BACKGROUND: Non-medical use of prescription drugs is a major public health concern in the United States. Prescription opioids and sedatives are among the most widely abused drugs and their combined use can be lethal. Increasingly rigid prescribing guidelines may contribute to the changing context of opioid use and increase drug diversion. OBJECTIVE: To examine gender differences in diversion of prescription opioids and sedatives among non-medical prescription opioid and sedative polysubstance users. We hypothesize that men will be more likely than women to engage in incoming diversion. METHODS: Data from the Prescription Drug Abuse, Misuse, and Dependence Study, a cross-sectional study focused on prescription drug users, were analyzed. Non-medical use was defined as use of a drug that was not prescribed or use in a way other than prescribed. Individuals who reported past 12-month non-medical opioid and sedative use were included; diversion was defined as incoming (obtaining drugs from a source other than a health professional) and outgoing (giving away/selling/trading prescription drugs). RESULTS: Among the 198 polysubstance users, 41.4% were female. Men were 2.85 times as likely as women to report incoming diversion (95% CI: 1.21–6.72). Women were more likely to obtain opioids from a healthcare professional; men were more likely to obtain sedatives from a roommate, coworker, or friend. Over half of men and women reported outgoing diversion opioids or sedatives. CONCLUSION: Drug diversion highlights an important point of intervention. Current prevention efforts that target prescribers should be expanded to include users and diversion activities; these interventions should be gender-specific.

Recent studies have shown that there are systematic differences among total and free prostate-specificantigen (PSA) immunoassays. In this study we analyzedintermethod differences in total PSA (tPSA) and free PSA(fPSA) measurement using ARCHITECT i2000SR (Abbott Diagnostics) and COBAS E601 (Roche Diagnostics). A number of 160 blood samples were tested for tPSA and 50 samples for fPSA (selecting only sampleswith tPSA: 4.1–10.0 μg/L). Passing–Bablok regression analysis was used to compare the two analytical methods fortPSA, fPSA and percentage of fPSA (%fPSA). A strong correlation was noticed between ARCHITECT i2000SR and COBAS E601 for tPSA, fPSA and %fPSA (r between 0.94 and 0.99). Concentrations of tPSA and fPSA measured by COBAS E601 were higher thanthose measured by ARCHITECT i2000SR with a bias of 0.8 μg/L for tPSA and 0.14 μg/L for fPSA. Analyzing therelative difference between methods for fPSA and %fPSA, COBAS E601 exceed a 10% relative difference limit. Our study confirms that there are differences in measured concentrations of tPSA and fPSA byvarious commercial methods. Because clinical judgment on subsequent diagnostic procedures, such as prostatebiopsy, is based on tPSA and fPSA results, tests harmonization should be a priority.

Non-medical use (NMU) of prescription opioids is of concern due to the opioid epidemic in the United States. Objective: We examined sex differences in the effect of age of first use of prescription...

Introduction Significance of serum uric acid (UA) in cerebrovascular disease still remains controversial. UA is most abundant natural antioxidant in human plasma. Its antioxidant properties might protect against free radical damage, thereby reducing the risk of oxidative stress-related cognitive impairment and dementia. Aim In our investigation, we determine the level of UA in 100 male patients diagnosed with the first ischemic brain stroke (blood samples were collected during the acute phase and post-acute phase), 100 male patients diagnosed with vascular dementia and 100 male healthy volunteers (control group). Methods UA was determined using DIMENSION LxR automatic analyzer. Measurement of UA concentration was based on an enzymatic method (range 208-428 μmol/L). Results The prevalence of hyperuricemia among ischemic stroke and vascular dementia patients was 30% and 8%, respectively. Serum UA concentration was higher 7 and 14 days after the stroke compared to the acute phase (24-48 hours after hospitalization) and these concentrations were significantly higher than those measured in the control group. UA levels measured at 24-48 hours after the first symptoms of ischemic stroke were strongly correlated with those measured after 7 days of treatment (r = 0.79, p = 0.001) or after 14 days (r = 0.839, p = 0.0049). No significant differences were found between ischemic stroke and vascular dementia groups. Conclusion UA concentrations were higher in ischemic stroke and vascular dementia groups than in controls. UA increase may reflect vascular atherosclerosis and tissue hypoxia. UA monitoring in patients with cerebrovascular disease is essential, because UA is more harmful than protective.

textabstractAlthough results of animal research show that interactions between stress and sex hormones are implicated in the development of affective disorders in women, translation of these findings to patients has been scarce. As a basic step toward advancing this field of research, we analyzed findings of studies which reported circulating cortisol levels in healthy women in the follicular vs. luteal phase of the menstrual cycle. We deemed this analysis critical not only to advance our understanding of basic physiology, but also as an important contrast to the findings of future studies evaluating stress and sex hormones in women with affective disorders. We hypothesized that cortisol levels would be lower in the follicular phase based on the proposition that changes in levels of potent GABAergic neurosteroids, including allopregnanolone, during the menstrual cycle dynamically change in the opposite direction relative to cortisol levels. Implementing strict inclusion criteria, we compiled results of high-quality studies involving 778 study participants to derive a standardized mean difference between circulating cortisol levels in the follicular vs. luteal phase of the menstrual cycle. In line with our hypothesis, our meta-analysis found that women in the follicular phase had higher cortisol levels than women in the luteal phase, with an overall Hedges’ g of 0.13 (p < 0.01) for the random effects model. No significant between-study difference was detected, with the level of heterogeneity in the small range. Furthermore, there was no evidence of publication bias. As cortisol regulation is a delicate process, we review some of the basic mechanisms by which progesterone, its potent metabolites, and estradiol regulate cortisol output and circulation to contribute to the net effect of higher cortisol in the follicular phase.

We recently reported that current smokers and those with COPD had higher airway epithelial cell expression of the angiotensin-converting enzyme-2 (ACE-2) viral entry receptor [1]. We thus read with great interest the work of Russo et al. [2] which proposes a mechanism for this finding, namely that this upregulation is mediated by nicotine exposure specifically through the α7 subtype of nicotine acetylcholine receptors (α7-nAChR). While exposure to increasing concentrations of nicotine caused epithelial cells to increase ACE-2 levels, subsequent gene silencing of α7-nAChR appeared to significantly dampen this response. A secondary transcriptome sequencing analysis of our cohort (consisting of 42 subjects who underwent bronchoscopy for epithelial cell brushings [1]) reveals evidence in support of this hypothesis. We found that airway epithelial cell expression of CHRNA7, encoding α7-nAChR, was significantly correlated with the expression of ACE2 (fig. 1, Pearson r=0.54, p=2.31×10−8). There was significantly higher CHRNA7 expression in those with COPD (2.75±0.73 versus 2.14±0.43 in those without COPD, p=1.47×10−4), with a trend towards higher expression in current smokers compared to former and never smokers (2.86±0.92 in current smokers, 2.35±0.57 in former smokers, and 2.27±0.45 in never smokers, p=6.16×10−2). CHRNA7 was also negatively correlated with forced expiratory volume in 1 s percent predicted (Pearson r=−0.37, p=2.83×10−4). Interestingly, CHRNA7 was positively if weakly correlated with body mass index (Pearson r=0.14, p=6.31×10−3), raising the intriguing possibility that nicotine receptor mediation of ACE-2 may also be related to why obese individuals have made up a considerable proportion of COVID-19 cases [3]., α7-nAChR may upregulate ACE-2

Introduction: The dietary supplements are defined as vitamins and minerals or herbal products and are typically given in the form of a capsule or tablet. The nonsmokers are more attempted to use dietary supplements than individuals who smoke. Aim: In our investigation, we examined associations between vitamin B, folic acid, multivitamin or mineral intake among the student population and their correlation with smoking prevalence and drinking coffee. Materials and methods: We used a questionnaire to examine the general characteristics of the subjects, age, sex, their lifestyle, cigarette smoking, coffee intake and their use of dietary supplements. Data were collected from participants of the University of Sarajevo and a longitudinal study of 960 men and women aged 18-24 years from 2017 to 2018 was conducted. Results: The results showed that 32% of students took vitamin B supplements and 10% folic acid. In opposite, more than half of students took multivitamins (59.5%) and minerals (60.4%) less than one year. About a quarter or less took multivitamins (23.9%) and minerals (24.3%) for years. Less than 20% of students took multivitamins and minerals within a period of one year. In student population smoking prevalence was estimated at 21.2% and coffee intake in 71.2%. The smoking and use of vitamin B supplements were independent of each other, p = 0.201. The use of folic acid did not depend on smoking p = 0.501. There were no observed correlations between multivitamin and mineral supplement consumption compared to smoking status or drinking coffee. Conclusion: Deficient dietary intake of folic acid and B vitamins from food and supplemental sources appear to be one of the atherosclerosis incidences. Further studies should examine associations between dietary supplements intake and lifestyle of students, as well as smoking status and coffee intake.

Introduction: Carcinoembryonic antigen (CEA) is used for monitoring of disease progression and treatment response in cancer patients. Our aim was to compare the performance of chemiluminescent microparticle immunoassay (CMIA) with electrochemiluminescence immunoassay (ECLIA) for CEA. Methods: A total of 115 samples were collected during routine diagnostic, prognostic and therapy monitoring procedures in patients with colorectal and pancreatic cancer. We used ARCHITECT i2000SR and Cobas E601 for CEA analysis in sera samples. Results: The correlation coefficient of 0.984 [95% CI: 0.972 to 0.991] for results obtained on both platforms was observed for CEA≤10 ng/mL group. Moreover, intercept of 0.9027 [95% CI: 0.705 to 1.099] and slope 0.8076 [95% CI: 0.765 to 0.8498] (p < 0.0001) was observed in this group. In CEA >10 ng/mL group we observed slope = 1.1986 [95%CI: 1.1474 to 1.2498] (p < 0.0001), intercept = -11.69 [-17.53 to - 5.84] and correlation coefficient of 0.985 [95% CI: 0.976 to 0.9914]. Mean differences between assays in group ≤10 ng/mL and >10 ng/mL were 0.2066 (95% CI: 0.0019 to 0.4113) and –2.66 (95% CI: -10.10 to 4.76) ng/mL, respectively. Conclusion: Although there were differences, based on 20 days precision tests, overall results showed a good analytical performance and correlation between CEA assays on ARCHITECT i2000SR and Cobas E601 platforms. Reference intervals appropriate for the method of CEA measurement should be used. The standardization and harmonization of serum CEA concentration assays are needed.

Introduction: In the present study we investigated the performance, precision, and recovery of three different automated methods in determining cancer antigen (CA) 15-3 levels.Methods: Serum samples were obtained from 60 hospitalized female patients. As controls, commercially available samples were used. Cancer antigen (CA) 15-3 levels were measured using ARCHITECT CA 15-3, Elecsys® CA 15-3, and Vitros CA 15-3 immunoassays. A comparison of the results between the three methods was conducted, and the precision and recovery were analyzed.Results: Coefficient of variations (CVs), determined with low- and high-level-CA 15-3 control samples, and reproducibility values were: 2.56-2.80% and 3.10-4. 20% for ARCHITECT i2000SR immunoassay analyzer; 3.50-5.55% and 4.88-6.47% for Cobas E 601 analyzer; 3.30-4.0% and 4.30-4.80% for VITROS 5600 Integrated System, respectively. The percent recoveries were 95-98% for Elecsys® CA 15-3 assay, 93-105% for Vitros CA 15-3 assay, and 92-95% for ARCHITECT CA 15-3 assay. Method comparison results demonstrated correlation coefficient (r) in range from 0.994 to 1. The average CA 15-3 concentrations measured by Vitros, ARCHITECT, and Elecsys® were 157.24 +/- 329.75 U/mL, 100.91 +/-213.75 U/mL, and 80.93 +/- 173.29 U/mL, respectively.Conclusions: Tumor marker CA 15-3 in individual patients should be monitored using the same immunoassay method, reagents, and analyzer. Different immunoassays tested on different analyzers, often show large discrepancies in reported values for individual patients. Different immunoassay technologies quantify analytes of clinical interest using monoclonal or polyclonal antibodies. Thus, the usage of antibodies with different specificities could explain the differences in CA 15-3 serum values between different methods.

As the number of older adults in low- and middle- income (LMIC) countries is expected to grow substantially over the next several decades, it is important to develop programs for the prevention of major depression in later life. These programs should be flexible enough to be adjusted to the needs of poorly resourced LMICs. The current report provides an overview of a “depression in later life” (DIL) study in Goa, India, as a promising and effective mental health prevention program, with the potential for implementation in other LMICs. DIL study uses unspecialized physicians and lay health counselors (LHCs) to deliver both scalable psychological intervention and low-intensity intervention, consistent with Institute of Medicine’s (IOM, 1994) indicated prevention approach. DIL intervention led to reduced incidence of Major Depressive Disorder in DIL-randomized participants and as such it is important in meeting the 2016-2030 United Nations Sustainable Development Goal of “Ensuring healthy lives and promoting the well-being for all at all ages."

Objective The current analysis examines whether opioid use is associated with insomnia in a community sample, as the consequences of the growing epidemic of prescription opioid use continue to cause public health concern. Study design A cross-sectional study including 8433 members in a community outreach program, HealthStreet, in Northeast Florida. Methods Community Health Workers (CHWs) assessed health information, including use of opioids (i.e., Vicodin®, Oxycodone, Codeine, Demerol®, Morphine, Percocet®, Darvon®, Hydrocodone) from community members during field outreach. Insomnia was determined based on self-report: “Have you ever been told you had, or have you ever had a problem with insomnia?” Summary descriptive statistics were calculated and logistic regression modeling was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals for insomnia, by opioid use status, after adjustment for demographics and other covariates. Results Among 8433 community members recruited (41% male; 61% Black), 2115 (25%) reported insomnia, and 4200 (50.3%) reported use of opioids. After adjusting for covariates, opioid users were significantly more likely to report insomnia than non-users (adjusted OR, 1.42; 95% CI, 1.25–1.61). Conclusion Insomnia was 42% more likely among those who reported using prescription opioids compared to those who did not. With one half of the sample reporting prescription opioid use, and a fourth reporting insomnia, it is important to further investigate the relationship between the two. Findings provide useful preliminary information from which to conduct further analyses.

Background: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. Methods: In a population-based cohort in The Netherlands (2002–2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9–20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. Results: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism–based heritability of overall motor development was 20% (SE =.21) and of autistic traits was 68% (SE =.26). The genetic correlation between overall motor development and autistic traits was.35 (SE =.21, p Conclusions: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

Recent evidence shows that COVID-19 patients with existing metabolic disorders, such as diabetes and metabolic syndrome, are exposed to a high risk of morbidity and mortality. At the same time, in order to manage the pandemic, the health authorities around the world are advising people to stay at home. This results in decreased physical activity and an increased consumption of an unhealthy diet, which often leads to an increase in body weight, risk for diabetes, insulin resistance, and metabolic syndrome, and thus, paradoxically, to a high risk of morbidity and mortality due to COVID-19 complications. Here we summarize the evidence demonstrating that the promotion of a healthy life style, including physical activity and a dietary intake of natural polyphenols present in coffee and tea, has the potential to improve the prevention and management of insulin resistance and diabetes in the time of COVID-19 pandemic. Particularly, it would be pertinent to evaluate further the potential positive effects of coffee beverages, rich in natural polyphenols, as an adjuvant therapy for COVID-19, which appear not to be studied sufficiently.

Objectives Cocaine use is increasing and many cocaine users engage in polysubstance use. Within polysubstance use, relationships among use of individual substances are necessarily complex. To address this complexity, we used latent class analysis (LCA) to identify patterns of polysubstance use among lifetime cocaine users and examine associations among these patterns, demographics, and risk profiles. Methods Members of HealthStreet, an ongoing community engagement program, were asked about lifetime and past 30-day use of cocaine, alcohol, tobacco, marijuana, and prescription medications, mental health conditions, recent Emergency Department (ED) visits and demographics. LCA was used to identify classes of past 30-day polysubstance use among individuals who endorsed lifetime cocaine use. Multinomial logistic regression identified factors associated with these classes. Results Among 1797 lifetime cocaine users, a five-class LCA model was identified: 1) past 30-day tobacco use only (45%), 2) past 30-day alcohol, marijuana and tobacco use (31%), 3) past 30-day tobacco, prescription opioid and sedative use (13%), 4) past 30-day cocaine, alcohol, marijuana and tobacco use (9%), 5) past 30-day cocaine and multiple polysubstance use (2%). Demographics, ED visits and mental health conditions were associated with class membership. Conclusions Approximately 11% of lifetime cocaine users used cocaine in the past 30 days with two different concurrent substance use patterns. Prescription medication (opioids and sedatives) and complex polysubstance use patterns were stronger indicators of negative outcomes than current cocaine use. Cocaine was not used frequently with other stimulants. In addition to polysubstance use, prescription medication use should be targeted for intervention among lifetime cocaine users., Highlights • Among 1,797 lifetime cocaine users, a five-class LCA model was identified. • Approximately 11% of lifetime cocaine users used cocaine in the past 30 days with two different polysubstance use patterns. • Opioid and sedative use and complex polysubstance use patterns were strong indicators of negative outcomes. • Cocaine was not used frequently with other stimulants.

Introduction: Dietary supplements are an important source of vitamins and minerals that may help prevent several disease-causing biological pathways involved in one-carbon metabolism, including the suppression of cell proliferation, oxidative stress, nitric oxide synthesis, and angiogenesis. The present study aimed to assess the association between the intake of folate, Vitamin B6, Vitamin B12, and minerals and the consumption of alcohol among university students. Methods: This study was participated by students aged 19-22 years from the University of Sarajevo between 2017 and 2018. Using a questionnaire, we interviewed in a week them to collect information regarding age, socio-economic status, alcohol consumption, and dietary supplement intake. Then, we investigated the association between the baseline intake of folate, B vitamins, and minerals and that of alcohol consumption. Results: Most students consumed Vitamin B supplements (32%) and folic acid (10%). Dietary multivitamins and minerals were less prevalent in more than a year, accounting for 186 (23.9%) and 174 (24.3%) students, respectively, than those in less than a year. In a year, 0.05). Conclusion: An extremely low percentage of the participating students in Canton Sarajevo used dietary supplements of Vitamin B, folate, multivitamins, and minerals. Moreover, alcohol consumption and dietary supplement intake were not associated. Further research is needed to establish the best cost-effective public health system to achieve a sufficient intake of dietary supplements.

Wastewater process models are the essential tools for understanding relevant aspects of wastewater treatment system. Wastewater process modeling provides more options for upgrades and better understanding of new plant design, as well as improvements of operational controls. The software packages (BioWin, GPS-X, Aqua designer, etc) solve a series of simulated equations simultaneously in order to propose several solutions for a specific facility. Research and implementation of wastewater process modeling in combination with computational fluid dynamics enable testing for improvements of flow characteristics for WWTP and at the same time exam biological, physical, and chemical characteristics of the flow. Application of WWTP models requires broad knowledge of the process and expertise in modeling. Therefore, an efficient and good modeling practice requires both experience and set of proper guidelines as a background.

Schizophrenia and bipolar disorder (BD) are heritable disorders with similarities in clinical symptoms and typical onset after puberty. While research shows that impaired motor coordination can have an associationwith schizophrenia, there are limited data on childhood development preceding BD. Murray et al proposed a developmental model for similarities and dissimilarities between schizophrenia and BD, but it remains unknown if dissimilarities exist in early infancy and if they covary with genetic liability for these disorders. Using polygenic risk scores (PRSs),we exploredwhether genetic risk for schizophrenia and genetic risk for BD are associated with neuromotor development in infancy.

Introduction: A progress in the management of cardiovascular disease leads to a decrease in mortality, but heart failure (HF) seems to be an exception. Today, the rate of rehospitalization and mortality after acute heart failure is still very high. Lower ejection fraction (EF) means worse prognosis, but recent studies are reporting that HF patients with preserved EF have no better survival compared to patients with reduced EF1. Goal: to investigate a possible difference in the outcome of HF patients with reduced (HFREF) and preserved ejection fraction (HFPEF). Patients and Methods: In 222 patients hospitalized in acute HF (138 with reduced EF and 74 with preserved EF) were determined routine laboratory test, including BNP. The LVEF cutoff for diagnosing of HFPEF was above 45 %. Patients were followed for the next 18 months for the occurrence of 1. readmission due to repeat decompensation and 2. mortality. Results: BNP at discharge was higher in HFREF compared to HFPEF group [699.3 (271.8-1519.1) pg/ml vs 263.3 (134.4-502.2) pg/ ml, p

With the increase in Internet use throughout the world, expansion in network security is indispensable since it decreases the chances of privacy spoofing, identity or information theft and bank frauds. Two of the most frequent network security breaches involve phishing and spam emails as they are an easy way to pass a virus or a malicious site, which can lead to extensive frauds. Despite the fact that there is an abundance of tools for detection and blocking of these types of messages and websites, society is still trying to combat and rise above said problem. The purpose of this paper was to exclude the human factor in security breaches executed in this manner with the use of various machine learning algorithms. For the purpose of training and testing of the most successful algorithms (Random Forest, k-Nearest Neighbor, Artificial Neural Network, Support Vector Machine, Logistic Regression, Naive Bayes) paper used two separate bases, UCIs Phishing Websites Data Set and Spam Emails Dataset together with Weka software, and found that the best results for both of them are achieved with the Random Forest algorithm. However, databases responded differently to feature selection algorithms, as the best result for phishing (97.33% accuracy) was accomplished through Ranker + Principal Components Optimization, and the best result for spam (94.24% accuracy) was accomplished through BestFirst + CfsSubsEval Optimization in Weka. These findings provide a base platform for future work towards a faster and more accurate online fraud detection.

Concurrent use of prescription medications and alcohol is prevalent among older adults and impacts women more than men, however little is known about characteristics of older women who use both. The current analysis aims to evaluate those characteristics. Participants were recruited through HealthStreet, an outreach program. Community health workers (CHWs) assess health needs and concerns among community members. CHWs collect demographic, substance use, and other health data from participants. Female participants (≥ 50 years) interviewed November 2011–November 2017 were included and stratified into four groups: neither prescription opioid nor hazardous alcohol use (three or more drinks in a single day), hazardous alcohol use only, prescription opioid use only, and both prescription opioid and hazardous alcohol use. Chi square and ANOVA tests were used to compare these groups. Among the 2370 women (53% black; mean age 61 years), 70% reported neither prescription opioid nor hazardous alcohol use, 12% reported hazardous alcohol use only, 15% reported prescription opioid use only, and 3% reported use of both in the past 30 days. Concurrent prescription opioid and hazardous alcohol use were significantly associated with comorbid depression and anxiety (p

To investigate the potential role of interleukin 4 (IL-4), interleukin 10 (IL-10) and high-sensitivity C-reactive protein (hs-CRP) as serum biomarkers of persistent/recurrent disease in papillary thyroid carcinoma (PTC) with/without Hashimoto's thyroiditis (HT).Eighty consecutive patients (64 F/16 M, 43.2 ± 12.7 years) with PTC and 40 (37 F/3 M, 40.6 ± 12.3 years) with papillary thyroid carcinoma associated with Hashimoto's thyroiditis (PTC + HT) were evaluated before radioiodine therapy. A control group of 20 patients with HT without thyroid cancer (18 F/2 M, 47.3 ± 2.8 years) was included in the study for the comparison of cytokine levels.No meaningful differences were found in clinical outcomes between PTC and PTC + HT groups (47.5% vs. 45% persistent/recurrent disease). Serum IL-4, IL-10 and hs-CRP levels were higher in patients with persistent/recurrent disease compared to those without recurrence (p0.001). IL-4, IL-10 and hs-CRP were also found in substantially higher concentrations in PTC + HT patients with persistent/recurrent disease than in patients with HT or PTC (with or without recurrence) (p0.01). Positive correlations were observed between IL-4, IL-10, hs-CRP and thyroglobulin (Tg) (r between 0.48 and 0.56, p0.005) or antithyroglobulin antibodies (TgAb) (r between 0.63 and 0.80, p0.002) in PTC and PTC + HT patients with persistent/recurrent disease.Increased levels of serum IL-4, IL-10 and hs-CRP are associated with persistent/recurrent disease in PTC and PTC + HT patients. Our results suggest that these biomarkers might be used to improve patient stratification according to the risk of recurrence, especially in patients with PTC + HT, where Tg levels are not reliable due to presence of TgAb.

Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-β1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter.Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically.IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P .001), and in persistent than in paroxysmal AF (P .001), in line with NT-proBNP and LA diameter. In contrast, TGF-β1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-β1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF).Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-β1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-β1 signaling pathway.

Background Renal insufficiency is one of the most serious renal diseases. Early diagnosis plays an essential role. Serum creatinine as a marker has had priority so far. The use of cystatin C for estimation of glomerular filtration rate has been recommended recently. There is a set of formulae which consolidates serum values of both creatinine and cystatin C. The study focuses on different formulae and their estimation for the purpose of better, faster, and more accurate diagnosis of renal insufficiency. Methods The sample consists of 75 examinees which are divided into three groups. The first group is made of patients with the glomerular filtration rate (GFR) 90 - 120 mL/minute/1.73m². The second group consists of patients with GFR 60 - 89 mL/minute/1.73m² and the third with GFR 30 - 59 mL/minute/1.73m². The exclusion criteria are the following: children and adolescents under the age of 20, pregnant women, patients on corticosteroid therapy and blockers of the distal tubular creatinine secretion. The five equations (GFR1-5) used in this research are: a Cockcroft-Gault equation - GFR1; a MDRD equation - GFR2; CKD-EPI - an equation based on cystatin C - GFR3; CKD-EPI - an equation based on cystatin C, adjusted according to the gender and age - GFR4; and CKDEPI - a combined equation based on cystatin C and creatitine, adjusted according to the age, gender, and race - GFR5. Upon acquiring the results, it is followed up with the statistical data analysis followed by graphs and tables. Results After data analysis, it is established that data distribution does not show normal distribution in each case, which leads to the use of nonparametric statistics. Depending on the stage of kidney injury there are different results regarding the difference in statistics of the used formulae. The highest sensitivity is recorded with the formulae GFR4 and GFR5. Then the increase in cystatin C levels increases sensitivity with the formulae GFR3 and GFR4. Conclusions As a result of this study, it is to be established that the formula of choice is the GFR3 - CKD-EPI formula based on serum cystatin C values, without adjustments. Its sensitivity, specificity, price, and feasibility are to be observed as parameters. Besides that, the increase in serum cystatin levels leads to the increase of sensitivity of the GFR3 formula, which could be an additional factor in the selection of formulae.

Recent literature focused on prescription opioids has neglected sex differences in use. Here, we evaluated the recent literature (since 2015) examining sex differences in prescription opioid use.Between 2015 and 2016, our review found only eight articles addressing sex differences in prescription opioid use mostly opioid misuse in North America among individuals with chronic pain. Risk factors included depression, pain, and polydrug use. In addition to that review, we had the opportunity to further address sex differences in, and risk factors for, prescription opioid use through a community engagement program, HealthStreet. Among the sample (n = 8525, Mage = 43.7 years, 58.6% women), approximately half reported use of prescription opioids. Women were significantly more likely to report lifetime use (54.9 vs. 42.2%; P 0.0001) and report cancer compared with men, yet, women with cancer had a significantly reduced risk of using opioids compared with men with cancer (odds ratio: 0.46; 95% confidence interval, 0.36-0.59).Only a few recently published studies analyzed sex differences related to prescription opioid use. Findings from the literature and our data suggest women are more likely to use prescription opioids compared with men. There is limited information on sex differences in opioid use risk factors and outcomes and more research in this area is warranted.

Introduction Idiopathic Idiopathic membranous nephropathy (iMN) is an immune-complex mediated renal disease which is usually associated with the nephrotic syndrome (NS). The course of the disease is variable. Some patients maintain normal kidney function with or without a spontaneous remission of proteinuria, while others progress to end-stage renal failure or die from complications related to the nephrotic syndrome. Whether or not to treat a patient with idiopathic membranous nephropathy is still controversial. The controversy is mainly related to the toxicity of the therapy and the variable natural course of the disease-spontaneous remission occurs in 40-50% of patients. Aim The aim of this study was to describe our experience of treatment of an idiopathic membranous nephropathy (iMN), efficacy and complications rate. Case report Our patient was older, mail gender, in high-risk group with persistent proteinuria 10,68 g/day and stable renal function. We have taken these factors into consideration, along with age and other comorbidities, that may significantly elevate the risk of treatment. We chose to start with early treatment, following the Ponticelli's group protocol based on high dose corticosteroids (odd months) alternating with clorambucil (even months) for six months. This treatment was accompanied by the steroid side effects, including hyperglycaemia dependance on insulin therapy and pulmonary thromboembolism despite administered prophylactically low molecular weight heparin. The six-month treatment was successfully completed with the reduction of proteinuria to nephritic values 2,86 g/day, despite many complications. Complete remission of the disease with non-significant proteinuria and with stable renal function was achieved in 14 months which has been maintained for 2 years. Conclusion We suggest that decisions on the timing of start of therapy, whom to treat, best sequence of the use of the various immunosuppressive drugs must be based on an individualized assessment of risks and benefits.

Introduction Symptomatic and etiopathologic heterogeneity of schizophrenia (SCH) and bipolar disorder (BD) can be adequately addressed using a dimensional approach to psychopathology, as well as interpreting physiological properties and markers as predictors of disease onset and relapse. Risk factors, genetic and environmental, are likely to modify the neurobiological processes characteristic of certain physiological processes that manifest to a greater degree of overlapping symptoms. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. It gives us an insight into the general somatic condition of the patient. It assesses the ability to transport oxygen to tissues and carbon dioxide back to the lungs via erythrocytes (RBC) and hemoglobin (HGB) as their most important constituents, and is also an indicator of iron status and blood oxygenation. Aim Schizophrenia (SCH) and bipolar disorder (BD) are psychiatric disorders whose complex etiology and pathogenesis are still far from known. A correlation between red blood cell abnormalities and these diseases has been recognized in some studies. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. However, so far there is a small number of published papers that relate to the relationship between laboratory parameters of blood and the aim of this paper is to reveal more light in this subject. Methods The research was done as an observational prospective clinical study that has evaluated different physiological and pathological parameters in patients with BD and SCH over a two-year period. A total of 159 patients with schizophrenia, 61 patients diagnosed with bipolar disorder and 82 healthy subjects participated in this study. Results At baseline, BD compared to SCH patients had higher mean lymphocyte count (2,6±0,7 vs. 2,0±0,6x109; p=0,006) and haemoglobin concentration (146,8±12,2 vs. 140,2±14,7 g/L; p=0,03), and significantly lower red cell distribution width (13,6±2,2 vs. 14,7±1,8%; p=0,008). In both BD and SCH patients there was a significant number of patients with low red blood cells count and low haemoglobin concentration, and high MCH and MCHC at baseline and at 3 and 6 months of follow up. Conclusions The finding that SCH as well as BD differed from controls with respect to red blood cells, hemoglobin, lymphocytes, and average platelet count was consistent with previous findings and could be understood as a qualitative measure in the evaluation of this sample. The fact that no association with other parameters was found, as well as an association with the diagnosis, does not exclude that these associations can be found in larger samples.

Background Morbidity and mortality attributed to prescription opioids are a crisis in the US and spreading globally. Sex differences related to these conditions have not been adequately assessed. Methods Through our community engagement program, data on demographics, health status, and substance use, including prescription opioids (e.g., Vicodin®, Oxycodone), were collected from community members in Florida (primarily North Central Florida) during a health needs assessment. Participants over 18 years of age were classified by opioid use: past 30-day, lifetime but not past 30-day, or no lifetime prescription opioid use. Descriptive statistics and chi-square tests were calculated, and multinomial logistic regression was used to calculate adjusted odds ratios (aOR; CI). Analyses were conducted for men and women separately to examine sex specific effects. Results Among 9221 community members assessed, the mean age was 45 years, 60% were female, and 58% were black. Respondents who endorsed past 30-day use and lifetime use were more likely to be female. Prescription sedative use was the strongest risk factor for past 30-day (aOR = 3.96; 95% CI, 3.35–4.68) and lifetime (aOR = 2.67; 95% CI, 2.34–3.04) prescription opioid use, regardless of sex. Other factors including marijuana use and history of cancer were significantly associated with prescription opioid use; they varied by sex. Conclusions The risk factors identified in this community sample provide additional information not accounted for by national studies. Future examinations of the consequences of concomitant opioid and sedative use, especially among women, are needed.

Motivational interviewing (MI) is an evidence-based psychotherapeutic approach to health behavior change and has great potential to improve medical regimen adherence among the older population. This article provides a concise summary of MI as it can be applied to geriatric patient populations. The goal is to provide readers with an overview of MI, its clinical applications within psychological and medical settings and its adaptation for use with older individuals dealing with both mental health and general medical conditions. The article also discusses how varied systemic and therapeutic contexts (e.g., biomedical vs. psychological) may affect the meaning and implementation of MI. Although published randomized controlled studies on the effects of MI in the older population are limited, the majority of such studies indicates that MI is effective in influencing change in health behaviors. As a proven, cost-efficient treatment, MI should be considered for clinical use in geriatric and primary care clinics pr...

Non-medical use (NMU) of prescription opioids in youth is of concern since they may continue this pattern into adulthood and become addicted or divert medications to others. Research into risk factors for NMU can help target interventions to prevent non-medical use of opioids in youth.The National Monitoring of Adolescent Prescription Stimulants Study (N-MAPSS) was conducted from 2008 to 2011. Participants 10-18years of age were recruited from entertainment venues in urban, rural and suburban areas of 10 US cities. Participants completed a survey including questions on their use of prescription opioids. NMU was defined as a non-labeled route of administration or using someone else's prescription. Information on age, gender, alcohol, marijuana and tobacco use was also collected. Summary descriptive, chi-square statistics and logistic regression were conducted using SAS 9.4.Of the 10,965 youth who provided information about past 30day prescription opioid use, prevalence of reported opioid use was 4.8% with 3.2% reported as NMU (n=345) and 1.6% as medical use (MU) only (n=180). More males than females (55.7% vs. 44.4%) reported opioid NMU (p0.0001). Logistic regression revealed that among males (comparing NMU to MU only), current smokers were 4.4 times more likely to report opioid NMU than non-smokers (95% CI: 1.8, 10.7). Among females (comparing NMU to MU only), current smokers and alcohol users were more likely to report opioid NMU than those who had never smoked or used alcohol (OR=3.2, 95% CI: 1.4, 7.0 and OR=4.1, 95% CI: 1.7, 10.4, respectively).These results suggest that further research on gender differences in opioid NMU is needed; interventions for opioid NMU may need to be gender specific to obtain the best results.

BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002–2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen’s Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children’s behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers’ report: β = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers’ report: β = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers’ report: β = .11; 95% CI: 0.05 to 0.18; fathers’ report: β = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

Introduction: Increased inflammatory markerscorrelate with progressive hypothyroidism. The link between subclinical hypothyroidism, subclinical inflammation and cardiovascular disease in postmenopausal women still remains unclear.

Introduction: The aim of this study was determination of troponin I at serum using Architect (Abbott) and AxSYM System (Abbott). Troponin is regulatory subunit of the troponin complex associate with actin filament within muscle cells and it is a marker for diagnosis of myocardial damage.Methods: We used Architect STAT chemiluminescent microparticle immunoassay (CMIA) and AxSYM microparticle Enzyme Immunoassay (MEIA), techniques for quantitative determination of cardiac TnI in human serum or plasma. At our study we have proved precision, reproducibility and accuracy from both methods. The investigation included patients (n=119) who have myocardial infarction or ischemic heart damage and were treated at cardiology, emergency, internal medicine and neurology unit in Clinical Center University in Sarajevo.Results: The precision for three controls using Architect STAT TnI asssay technology were 3.6 – 5.2 % and reproducibility was 3.7 to 5.6 %. The AxSYM STAT TnI has precision for three controls 4.3–6.6 % and reproducibilitywas from 4.8 to 7.8 %. We have got very good correlation between Architect and AxSYM technology r = 0.999 in the investigation of troponin I in serum.Conclusions: We can conclude that chemiluminescent troponin assay I (Architect) showed good analytical performance and gave new possibility at troponin I determination.

Background The long-term safety and tolerability of sildenafil treatment of pulmonary arterial hypertension (PAH) were assessed. Methods Two hundred fifty-nine of 277 randomized and treated patients completed a 12-week, double-blind, placebo-controlled trial (SUPER-1 [Sildenafil Use in Pulmonary Arterial Hypertension]) of oral sildenafil in treatment-naive patients with PAH (96% functional class II/III) and entered an open-label uncontrolled extension study (SUPER-2) that continued until the last patient completed 3 years of sildenafil treatment. Patients titrated to sildenafil 80 mg tid; one dose reduction for tolerability was allowed during the titration phase. Results The median duration of sildenafil treatment across SUPER-1 and SUPER-2 was 1,242 days (range, 1-1,523 days); 170 patients (61%) completed both studies, and 89 patients discontinued from SUPER-2. After 3 years, 87% of 183 patients on treatment were receiving sildenafil 80 mg tid. Of patients remaining under follow-up, 3%, 10%, and 18% were receiving a second approved PAH therapy at 1, 2, and 3 years, respectively. At 3 years post-SUPER-1 baseline, 127 patients had an increased 6-min walk distance (6MWD); 81 improved and 86 maintained functional class. Most adverse events were of mild or moderate severity. At 3 years, 53 patients had died (censored, n=37). Three-year estimated survival rate was 79%; if all censored patients were assumed to have died, 3-year survival rate was 68%. No deaths were considered to be treatment related. Conclusions Long-term treatment of PAH initiated as sildenafil monotherapy was generally well tolerated. After 3 years, the majority of patients (60%) who entered the SUPER-1 trial improved or maintained their functional status, and 46% maintained or improved 6MWD. Trial registry ClinicalTrials.gov; No.: NCT00159887; URL: www.clinicaltrials.gov

SUMMARYWe report an outbreak associated with a dinner cruise on Lake Michigan. This took place on the same day as heavy rainfall, which resulted in 42·4 billion liters of rainwater and storm runoff containing highly diluted sewage being released into the lake. Of 72 cruise participants, 41 (57%) reported gastroenteritis. Stool specimens were positive for Shigella sonnei (n=3), Giardia (n=3), and Cryptosporidium (n=2). Ice consumption was associated with illness (risk ratio 2·2, P=0·011). S. sonnei was isolated from a swab obtained from the one of the boat's ice bins. Environmental inspection revealed conditions and equipment that could have contributed to lake water contaminating the hose used to load potable water onto the boat. Knowledge of water holding and distribution systems on boats, and of potential risks associated with flooding and the release of diluted sewage into large bodies of water, is crucial for public health guidance regarding recreational cruises.

Introduction Electroencephalography can also be used to monitor long-term recovery of the patient after acute phase of the disease. Impaired neurocognitive function after infection, similar to brain injury, may present a transient but also prolonged problem for the functioning of an individual. Some studies have shown that importance of EEG may not be significant in sequel monitoring, because the extensive changes in EEG seen with severe forms of CNS infection do not necessarily imply a longer-term poor outcome. Aim To examine the predictive potential of electroencephalography (EEG) in regard to the emergence of neurological and cognitive sequelae of acute central nervous system (CNS) infection. Methods The study included 62 patients treated at the Clinic for Infectious Diseases, Clinical Center of Sarajevo University, who were diagnosed with acute CNS infection. The EEG record was characterized as: normal, non-specific changes of mild, moderate and severe degree and specific changes. The sequelae (headache, cognitive dysfunction, neurological and neurophysiological disorders, audiological and behavioral disorders) was evaluated by combining neurological, psychiatric, pediatric, otolaryngological, ophthalmic and infectological examination in the Neuroinfective Counseling Department for up to 6 months after discharge. Results After a treatment of an acute CNS infection 25 (40.3%) patients had no sequelae and 37 (59.7%) were with sequelae. The EEG in the initial stage of the disease (Wald's coefficient = 12.8), followed by the age of the patients (Wald = 6.4), had the greatest influence on the prediction of sequela (p=0.0001). For each additional degree of verified pathological changes in the EEG, the risk of sequelae was increased by 5 degrees (OR = 5.3), respectively. There was no statistically significant association between changes in cerebrospinal fluid (CSF) findings, meningeal symptoms, and signs with sequelae development. Conclusion Younger age, as well as severe clinical status of a patient, which implies a disorder of consciousness and seizures on admission, are associated with irreversible consequences on a previously mentally healthy individual. Pathological changes (Delta and Theta waves, spike slow complex wave) on the EEG finding significantly predicted presence of sequelae. .

Background: Schizophrenia (SCH) is a serious mental disorder, clinical syndrome, characterized with various psychopathological symptoms, composed of a series of psychological and behavioral symptoms. Over the past decades, great attention has been given to the treatment of schizophrenia and related psychotic disorders, and the focus is on a new class of antipsychotic drugs. Objective: The aim of this study was to evaluate variations in the pharmacological efficacy of typical (TA) and atypical antipsychotics (AA) prescribed in the treatment of schizophrenia using PANSS scale. Methods: The research was done as an retrospective-prospective clinical study that has evaluated different PANSS scores in patients with SCH over a two-year period. A total of 58 patients with schizophrenia, and 82 healthy subjects participated in this study. Results: Typical and atypical antipsychotics showed equal efficacy in reducing positive symptoms and there were no significant statistics difference between them (p> 0.005), but atypical antipsychotics showed greater efficacy in reducing of negative symptoms of SCH. Conclusion: We showed that both groups of drugs were equally effective in reducing positive symptoms of SCH, and that atypical antipsychotics were still statistically significantly more effective in reducing negative symptoms of SCH. The main observation of a statistically significant higher efficacy of atypical antipsychotics in our relatively small sample most likely speaks in favor of their superiority.

Introduction: Inadequate vitamin B 12, folate status and B6 are associated with an increased risk for chronic diseases that may have a negative impact on the health. Aim: The aim of our study was to investigate dietary intake of vitamin B12, B6 and folates from various foods among the university students. Methods: Dietary intake of foods having vitamins B12, B6 and folate was assessed among the students of University of Sarajevo, 19-22 years old, from 2017 to 2018. The participants were interviewed to collect information regarding age, socioeconomic status, B12, folate, B6 vitamin, and usual food intake during one week. Results: The main sources of vitamin B12 and B6 in the studentsÂ’ diet were chicken white meat (51.8-53.7 %), beef (45-63 %), cream (62.2 -72.1 %), sardines in oil (47.9-52.2 %), tuna (55.2 -60.4 %), cheese edamer (80.1%) and cheese feta (67.4%-73%). The foods with a high source of vitamin B12 and B6 but rarely consumed were fish, shellfish, salmon, roasted trout and mackerel. Sufficient folate intake was mainly achieved through dietary intake of beans (48.5-57.2%) and oatmeal (46.3-48.2%), while folate-insufficient diet resulted from intake of spinach (30.9-35 %), turkey (26.2-33.4 %), lentils (16.9-19.7 %) and soy (9.4-15.5%). Conclusion: Our results show that there is an important percentage of the students in Canton Sarajevo that do not meet the recommended intakes for vitamin B12 and B6 and folate. Additional research is needed to establish the best cost-effective public health approach to achieve sufficient intake of these vitamins.

In April 2009, following the first school closure due to 2009 pandemic influenza A (H1N1) (pH1N1) in Chicago, Illinois, area hospitals were inundated with patients presenting with influenza-like illness (ILI). The extent of disease spread into the surrounding community was unclear. We performed a household survey to estimate the ILI attack rate among community residents and compared reported ILI with confirmed pH1N1 cases and ILI surveillance data (ie, hospital ILI visits, influenza testing, and school absenteeism). The estimated ILI attack rate was 4.6% (95% confidence interval, 2.8%-7.4%), with cases distributed throughout the 5-week study period. In contrast, 36 (84%) of 43 confirmed pH1N1 cases were identified the week of the school closure. Trends in surveillance data peaked during the same week and rapidly decreased to near baseline. Public awareness and health care practices impact standard ILI surveillance data. Community-based surveys are a valuable tool to help assess the burden of ILI in a community.

BACKGROUND: In pulmonary arterial hypertension (PAH), adding oral sildenafil to intravenous epoprostenol improved 6-minute walk distance (6MWD) and hemodynamics and delayed time to clinical worsening in a 16-week randomized, placebo-controlled trial (Pulmonary Arterial Hypertension Combination Study of Epoprostenol and Sildenafil [PACES-1]). METHODS: Patients completing PACES-1 could receive sildenafil (titrated to 80 mg, three times daily, as tolerated) in an open-label extension study (PACES-2) for ≥ 3 years; additional therapy was added according to investigator judgment. Survival and changes from PACES-1 baseline in World Health Organization Functional Class and 6MWD were captured. RESULTS: In an open-label setting, 6MWD, an effort-dependent outcome measure, was known to have improved or to have been maintained in 59%, 44%, and 33% of patients at 1, 2, and 3 years, respectively; functional class was known to have improved or to have been maintained in 73%, 59%, and 46%. At 3 years, 66% of patients were known to be alive, 24% were known to have died, and 10% were lost to follow-up. Patients with PACES-1 baseline 6MWD < 325 meters without 6MWD improvement during the first 20 weeks of sildenafil treatment subsequently had poorer survival. CONCLUSIONS: Although reliable assessments of safety and efficacy require a long-term randomized trial, the addition of sildenafil to background intravenous epoprostenol therapy appeared generally to be well tolerated in PAH patients.

Summary Objective: Inhaled human insulin (Exubera®; EXU) has shown encouraging tolerability in short-term trials. We evaluated the safety profile of EXU after long-term exposure. Design: In two, open-label, 2-year studies patients poorly controlled on a sulphonylurea were randomised to adjunctive EXU or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2). Patients: The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated haemoglobin (HbA1c) levels of 8–12%. Measurements: Main outcome measures were pulmonary function tests and insulin antibody assays. Results: A total of 109 patients (study 1) and 195 patients (study 2) completed 104 weeks treatment. In both studies, small treatment group differences in change from baseline forced expiratory volume in 1 s were greatest at 6 months (first time-point measured) and less at later visits, and reversed on treatment discontinuation. At 2 years, differences in mean changes were −0.10 and −0.01 l in studies 1 and 2, respectively, and −0.04 l for the pooled studies. There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA1c or lung function changes. Glycaemic control was maintained over 2 years. Conclusions: Exubera was well tolerated during long-term use. Pulmonary function changes compared with comparator groups were small, non-progressive and reversed upon treatment discontinuation. Importantly, rates of lung function change were indistinguishable between EXU and comparator after 6 months of therapy.

Retrospective study was conducted in surgical intensive care unit (ICU) in Clinical Hospital Center Zagreb in 2005. The aim of study was to create guidelines for empirical antibiotic therapy of sepsis in ICU for unknown causative agent based on antimicrobial susceptibility of causative bacteria.Thirty-two patients with severe sepsis were included in study and from medical records their clinical and microbiological data were analyzed. Antimicrobial susceptibility of the strains isolated from the blood-culture was tested by disk diffusion method according to CLSI (Clinical Laboratory Standard Institution). We used APACHE II score to predict the severity of illness. Mann-Whitney test and χ2 test were used to test statistical significance difference between results.Acinetobacter baumannii and Pseudomonas aeruginosa were the predominant causative agent. Acinetobacter baumannii was displaying excellent susceptibility to ampicillin+sulbactam and carbapenems, whereas Pseudomonas aeruginosa was showed good susceptibility on ceftazidim and carbapenems. Methicillin-resistant Staphylococcus aureus (MRSA), third predominant causative agent exhibiting good susceptibility to vancomycin and linezolide.The recommended therapy is empirical antibiotic therapy and should cover all important pathogens.

The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immu-nohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence ofvascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p